LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS: 3-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 1 STUDY

BackgroundUpadacitinib (UPA) improved symptoms in patients (pts) with psoriatic arthritis (PsA) with prior inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (nbDMARD-IR) through week (wk) 104 or 2 years of treatment in SELECT-PsA 1 [1].ObjectivesTo evaluate efficacy and safety of UPA vs adalimumab (ADA) through wk 152 or 3 years from the ongoing long-term open-label extension of SELECT-PsA 1.MethodsPts were randomized to receive UPA 15 mg (UPA15) or UPA 30 mg (UPA30) once daily, ADA 40 mg (ADA) every other wk, or placebo (PBO). At wk 24, PBO pts switched to UPA15 or UPA30. Following approval of UPA15, the protocol was amended so pts on UPA30 switched to UPA15 (earliest at wk 104). Efficacy was assessed through wk 152, and safety through June 13, 2022.ResultsOf 1704 pts randomized, 911 completed 152 wks of treatment. The proportions of pts achieving.≥20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), minimal disease activity (MDA), and ≥75%/90%/100% improvement in Psoriasis Area and Severity Index at wk 152 were generally consistent with those at wk 1041. UPA had greater ACR20/50/70 and MDA responses vs ADA, and a greater mean change from baseline (BL) in Health Assessment Questionnaire-Disability Index, pt's assessment of pain, and Bath Ankylosing Spondylitis Disease Activity Index vs ADA. Change from BL in modified total Sharp/van der Heijde score were similar between UPA30 and ADA, and numerically higher with UPA15 (Table 1). The overall UPA safety profile remained unchanged (Figure 1) [1,2]. UPA had numerically higher rates of serious infection (SI), herpes zoster (HZ), anemia, lymphopenia, creatine phosphokinase (CPK) elevation, and non-melanoma skin cancer (NMSC) vs ADA. Increases for SI, HZ, anemia, and CPK elevation with UPA were dose dependent. Rates of major adverse cardiovascular events, venous thromboembolism, and malignancy excluding NMSC were low and generally similar across groups. The most common cause of death was COVID-19.ConclusionEfficacy of UPA in nbDMARD-IR pts with PsA was maintained through 3 years of treatment. No new safety signals were identified.References[1]McInnes IB, et al. Rheumatol Ther 2022;1–18 [Epub ahead of print].[2]McInnes IB, et al. RMD Open 2021;7(3):e001838.Table 1.Efficacy endpoints at wk 152UPA15 (n=429)UPA30a (n=423)ADA (n=429)Proportion of pts (%)NRIAONRIAONRIAOACR20/50/7064.6/52.0/35.9*89.8/71.6/ 48.263.1/54.1*/ 35.787.9/74.4/ 47.861.1/46.6/ 28.786.2/65.2/ 39.8Minimal disease activity37.555.143.5*60.335.950.2PASI75/90/100b50.5/42.5/32.269.2/58.5/ 43.458.1/46.7/3 7.678.6/63.5/ 50.954.0/40.8/ 30.379.6/59.9/ 44.6Resolution of enthesitis by Leeds Enthesitis Indexc50.475.248.973.846.077.0Resolution of dactylitis by Leeds Dactylitis Indexd65.495.266.197.965.497.1Change from BLeMMRMAOMMRMAOMMRMAOHealth Assessment Questionnaire- Disability Index-0.51-0.55-0.53*-0.58-0.45-0.49Pt's assessment of pain (numeric rating scale)-3.3*-3.5-3.3*-3.6-2.8-3.0Bath Ankylosing Spondylitis Disease Activity Indexf-3.09-3.27-3.16-3.54-2.81-2.71Modified total Sharp/van der Heijde score0.210.190.050.040.090.09aFollowing a protocol amendment, all pts on UPA30 switched to UPA15 (earliest switch at wk 104);data are presented by originally randomized group. bPts with psoriasis affecting ≥3% of body surface area at BL. cPts with LEI >0 at BL;resolution LEI=0. dPts with LDI >0 at BL;resolution LDI=0. eData shown as MMRM (least squares mean) and AO (mean). fPts with psoriatic spondylitis at BL. n value ranges: UPA15 (99–429), UPA30 (95–423), ADA (89–429). Nominal *p<0.05 UPA vs ADA.ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria;ADA, adalimumab;AO, as observed;BL, baseline;MMRM, mixed effect model repeated measurement;NRI, non-responder imputation;PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index;pt, patient;UPA15/30, upadacitinib 15/30 mg once daily;wk, weekAcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Carl Davies, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsIain McInnes Grant/research support from: AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Evelo, Causeway Therapeutics, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Koji Kato Employee of: AbbVie and may hold stock or options, Marina Magrey Consultant of: BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, and UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Celgene, Dermavant, Eli Lilly, EMD Sorono, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Grant/research support from: AbbVie, Adiga Life Sciences, Amgen, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, UCB;and has received honoraria or other fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, and UCB Pharma, Yihan Li Employee of: AbbVie and may hold stock or options, Yanxi Liu Employee of: AbbVie and may hold stock or options, Jianzhong Liu Employee of: AbbVie and may hold stock or options, Ralph Lippe Employee of: AbbVie and may hold stock or options, Peter Wung Employee of: AbbVie and may hold stock or options.

EFFECT OF UPADACITINIB ON REDUCING PAIN IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS AND INADEQUATE RESPONSE TO BIOLOGIC THERAPY

BackgroundPain is a debilitating symptom of ankylosing spondylitis (AS) that negatively affects patients' lives. Upadacitinib (UPA), a Janus kinase inhibitor approved for the treatment of AS and other inflammatory diseases, showed significant efficacy vs placebo (PBO) in the phase 2/3 SELECT-AXIS 1 study in patients with AS who were biologic-naive and in the phase 3 SELECT-AXIS 2 study in patients with active AS who had an inadequate response (IR) to biological therapy [1,2]. Improvement in pain outcomes with UPA was also previously demonstrated in the SELECT-AXIS 1 study [3].ObjectivesThe objective of this post-hoc analysis of SELECT-AXIS 2 was to evaluate the efficacy of UPA vs PBO on multiple pain assessments through 14 weeks in patients with IR to a biologic disease-modifying antirheumatic drug (bDMARD-IR).MethodsSELECT-AXIS 2 (NCT04169373) enrolled adults with active AS with IR to biological therapy, including patients who discontinued biologics due to lack of efficacy or intolerance [1]. Patients were randomized 1:1 to UPA 15 mg once daily (QD) or PBO for 14 weeks. Pain endpoints evaluated here included the proportion of patients achieving ≥30%, ≥50%, and ≥70% reduction from baseline, minimal clinically important difference (MCID, defined as ≥1 point reduction or ≥15% reduction from baseline), and much better improvement (MBI, defined as ≥2 point reduction and ≥33% reduction from baseline) in Patient's Global Assessment (PGA) of pain, total back pain, and nocturnal back pain on a 0–10 numeric rating scale [3,4]. Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.ResultsA total of 211 patients received UPA 15 mg QD and 209 patients received PBO. Higher proportions of patients receiving UPA vs PBO achieved ≥30% and ≥50% reductions in PGA of pain, total back pain, and nocturnal back pain as early as week 2 that were sustained at all time points through 14 weeks (nominal P<0.05;Figure 1a-c). Achievement of ≥70% reductions in PGA of pain and nocturnal back pain were higher at week 4 and sustained thereafter (Figures 1a and 1c), and achievement of ≥70% reduction in total back pain was higher at week 2 and week 8, but not week 4, and sustained thereafter (Figure 1b). Results were similar for the proportion of patients achieving MCID and MBI, with improvements in PGA of pain, total back pain, and nocturnal back pain for UPA vs PBO as early as week 1 (MCID) or week 2 (MBI) that were sustained through week 14 (all nominal P<0.001;Table 1).Table 1.Achievement of MCID and MBI in Pain Outcomes at Week 14 (NRI-MI)Responder Rate (95% CI), %Pain OutcomesUPA 15 mgPBONominal P ValuePGA of painMCID81.0 (75.8–86.3)62.7 (56.1–69.2)<0.0001MBI60.7 (54.1–67.3)24.9 (19.0–30.7)<0.0001Total back painMCID80.1 (74.7–85.5)65.1 (58.6–71.5)0.0005MBI58.3 (51.6–64.9)25.4 (19.5–31.3)<0.0001Nocturnal back painMCID82.9 (77.9–88.0)61.3 (54.7–67.9)<0.0001MBI61.6 (55.0–68.2)32.1 (25.7–38.4)<0.0001MBI, much better improvement;MCID, minimal clinically important difference;NRI-MI, non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19;PBO, placebo;PGA, Patient's Global Assessment;UPA, upadacitinib.ConclusionIn patients with active AS who were bDMARD-IR, greater proportions of patients treated with UPA achieved rapid and clinically meaningful reductions in pain vs PBO as early as week 2 that were sustained through 14 weeks across multiple pain assessments.References[1]van der Heijde D, et al. Ann Rheum Dis. 2022;81(11):1515-1523.[2]van der Heijde D, et al. Lancet. 2019;394(10214):2108-2117.[3]McInnes IB, et al. RMD Open. 2022;8(1):doi:10.1136/rmdopen-2021-002049.[4]Salaffi F, et al. Eur J Pain. 2004;8(4):283-291.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this p blication. No honoraria or payments were made for authorship. Medical writing support was provided by M. Hovenden and J. Matsuura of ICON plc (Blue Bell, PA, USA) and was funded by AbbVie.Disclosure of InterestsXenofon Baraliakos Consultant of: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, Galapagos, Janssen, Celgene, and Amgen, Grant/research support from: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, Galapagos, Janssen, Celgene, and Amgen, Marina Magrey Consultant of: UCB, Novartis, Eli Lilly, Pfizer, and Janssen, Grant/research support from: Amgen, AbbVie, BMS, and UCB Pharma, Louis Bessette Speakers bureau: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Organon, and Sanofi, Grant/research support from: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, and Gilead, Kurt de Vlam Speakers bureau: Amgen, Celgene, Eli Lilly, Galapagos, Novartis, and UCB, Consultant of: Amgen, AbbVie, Celgene, Eli Lilly, Galapagos, Novartis, and UCB, Grant/research support from: Amgen, UCB, and MSD, Tianming Gao Shareholder of: AbbVie, Employee of: AbbVie, Anna Shmagel Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Ana Biljan Shareholder of: AbbVie, Employee of: AbbVie, Victoria Jasion Shareholder of: AbbVie, Employee of: AbbVie, Peter C. Taylor Speakers bureau: AbbVie, Consultant of: Lilly, AbbVie, Pfizer, Galapagos, Gilead, Janssen, GlaxoSmithKline, Sanofi, Fresenius, Nordic Pharma, UCB, and Biogen, Grant/research support from: Galapagos.

BIMEKIZUMAB MAINTAINED IMPROVEMENTS IN EFFICACY ENDPOINTS AND HAD A CONSISTENT SAFETY PROFILE THROUGH 52 WEEKS IN PATIENTS WITH NON-RADIOGRAPHIC AND RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: RESULTS FROM TWO PARALLEL PHASE 3 STUDIES

BackgroundBimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, met all primary/secondary endpoints at Week (Wk) 16 in patients (pts) with active non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axSpA (r-axSpA;i.e., ankylosing spondylitis), in the parallel phase 3 BE MOBILE 1 and 2 studies, respectively.[1,2]ObjectivesTo assess efficacy and safety of BKZ in these pts up to Wk 52.MethodsBE MOBILE 1 (NCT03928704) and 2 (NCT03928743) both involved a 16-wk placebo (PBO)-controlled and 36-wk maintenance period.[1,2] Pts were randomised to subcutaneous BKZ 160 mg Q4W (BKZ) or to PBO then BKZ from Wk 16 (PBO/BKZ).Results220/254 (86.6%) randomised pts with nr-axSpA and 298/332 (89.8%) with r-axSpA completed Wk 52. Efficacy was sustained to Wk 52 in both studies (Table 1). ASAS40 responses in BKZ-randomised pts increased from Wk 16 (nr-axSpA: 47.7%;r-axSpA: 44.8%;non-responder imputation [NRI]) to Wk 52 (60.9%;58.4%;NRI) with high levels of efficacy across TNFi-naïve and TNFi-IR populations (Table 1). At Wk 52, ASDAS <2.1 was achieved by 61.6% and 57.1%, and ASDAS <1.3 by 25.2% and 23.4%, of BKZ-randomised pts with nr-axSpA and r-axSpA, respectively (Figure 1). Wk 16 reductions from baseline in objective signs of inflammation (MRI, hs-CRP), and improvements in function (BASFI) and ASQoL, were maintained through 52 wks. Efficacy at Wk 52 was similar in PBO/BKZ-treated and BKZ-randomised pts (Table 1).At Wk 52, 75.0% (183/244) of pts with nr-axSpA and 75.5% (249/330) of pts with r-axSpA had ≥1 treatment-emergent adverse event (TEAE) on BKZ;the most frequent (% pts) TEAEs by preferred term (MedDRA v19.0) were nasopharyngitis (nr-axSpa: 12.3%;r-axSpA 9.1%) and upper respiratory tract infection (9.4%;6.4%);few COVID-19 infections were reported (7.0%;2.1%). Incidence (pts/100 pt years) of serious TEAEs were low (4.4;7.1);no major adverse cardiovascular events, active tuberculosis cases, serious COVID-19 infections, or deaths were reported. Most incidences of fungal infection (19.6;14.9;none serious or systemic) were Candida (12.8;8.3) and mild to moderate;two pts in both studies discontinued the study due to Candida infections. Incidence of IBD (1.0;1.0) and uveitis (1.5;2.4) were low.ConclusionAcross the axSpA spectrum, BKZ resulted in sustained efficacy to Wk 52. No new safety signals were observed, consistent with the Wk 24 safety profile.[1,2]References[1]Deodhar A. Ann Rheum Dis 2022;81:772–3;2.[2]van der Heijde D. Ann Rheum Dis 2022;81:12–3.Table 1.Efficacy at Wk 52Mean (SE), unless statedBE MOBILE 1BE MOBILE 2PBO→BKZ N=126BKZ N=128PBO→BKZ N=111BKZ N=221ASAS40 [NRI] n (%)64 (50.8)78 (60.9)76 (68.5)129 (58.4)ASAS40 in TNFi-naïve [NRI] n (%)58 (53.2)a73 (61.9)b67 (71.3)c108 (58.7)dASAS40 in TNFi-IRe [NRI] n (%)6 (35.3)f5 (50.0)g9 (52.9)f21 (56.8)hASAS20 [NRI] n (%)88 (69.8)94 (73.4)89 (80.2)158 (71.5)ASAS PR [NRI] n (%)38 (30.2)38 (29.7)41 (36.9)66 (29.9)ASAS 5/6 [NRI] n (%)65 (51.6)71 (55.5)74 (66.7)124 (56.1)BASDAI CfB [MI]–3.5 (0.2)–3.9 (0.2)–4.0 (0.2)–3.6 (0.1)BASFI CfB [MI]–2.6 (0.2)–3.0 (0.2)–2.8 (0.2)–2.8 (0.1)ASDAS-MI [NRI] n (%)37 (29.4)47 (36.7)49 (44.1)71 (32.1)Nocturnal spinal pain CfB [MI]–4.1 (0.2)–4.3 (0.3)–4.6 (0.3)–4.1 (0.2)ASQoL CfB [MI]–5.3 (0.4)–5.9 (0.4)–5.6 (0.4)–5.7 (0.3)SF-36 PCS CfB [MI]11.4 (0.9)12.2 (0.9)12.3 (0.9)12.0 (0.6)BASMI CfB [MI]–0.4 (0.1)–0.6 (0.1)–0.7 (0.1)–0.7 (0.1)Total resolution of enthesitisi [NRI] n (%)41 (44.6)j51 (54.3)c31 (46.3)k67 (50.8)lASDAS-CRP CfB [MI]–1.6 (0.1)–1.8 (0.1)–1.9 (0.1)–1.7 (0.1)SPARCC MRI SIJ score CfB [OC]mMean (SD)–6.4 (10.7)n–7.6 (10.5)o–2.8 (6.1)p–4.7 (8.2)qBerlin MRI spine score CfB [OC]mMean (SD)–0.4 (2.0)k–0.7 (2.5)r–2.1 (3.4)p–2.4 (3.9)shs-CRP, mg/L [MI] Median2.21.72.02.3RS. n: a109, b118, c94, d184;eMax 1 TNFi;n: f17, g10, h37;iMASES=0 in pts with MASES >0 at BL;n: j92, k67;l132;mMRI sub-study;n: n70, o82, p48, q90, r79, s89.AcknowledgementsThis study was funded by UCB Ph rma. Medical writing support was provided by Costello Medical, funded by UCB Pharma.Disclosure of InterestsXenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Atul Deodhar Speakers bureau: Janssen, Novartis and Pfizer, Consultant of: AbbVie, Amgen, Aurinia, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Eli Lilly, Novartis, Pfizer and UCB Pharma, Employee of: Director of Imaging Rheumatology BV, Marina Magrey Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie and UCB Pharma, Walter P Maksymowych Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie and Pfizer;educational grants from AbbVie, Janssen, Novartis and Pfizer, Employee of: Chief Medical Officer for CARE ARTHRITIS, Tetsuya Tomita Speakers bureau: AbbVie, Astellas, BMS, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Novartis and Pfizer, Consultant of: AbbVie, Eli Lilly, Gilead, Novartis and Pfizer, Huji Xu Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Beigene, BioMap, IASO, Pfizer and UCB Pharma, Employee of: Clinical investigator for Peking-Tsinghua Center for Life Sciences, Marga Oortgiesen Shareholder of: UCB Pharma, Employee of: UCB Pharma, Ute Massow Employee of: UCB Pharma, Carmen Fleurinck Employee of: UCB Pharma, Alicia Ellis Employee of: UCB Pharma, Thomas Vaux Employee of: UCB Pharma, julie smith Employee of: UCB Pharma, Alexander Marten Employee of: UCB Pharma, Lianne S. Gensler Consultant of: AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: Novartis and UCB Pharma paid to institution.